State of the Network Ian McGowan & Sharon Hillier Annual Meeting March 14th, 2016 HIV Infection in the US HIV Infection in US MSM HIV Infection in US Women Global HIV Infection HIV Incidence Rates in ASPIRE & RING Studies ASPIRE Study RING Study 10 8 6 4 2 HIV Incidence Rates (%) Rates Incidence HIV 0 <21 years > 25 years 18-21 years22-26 years27-45 years 21-25 years The PrEP Landscape in 2016 (1) • Oral PrEP – Optimization of Truvada delivery – Increasing availability – US, Canada, France, South Africa, Kenya, Israel – 2nd generation regimens being evaluated • Maraviroc combinations • Tenofovir alafenamide – New molecules • EFdA (Merck) The PrEP Landscape in 2016 (2) • Injectable PrEP – Rilpivirine & Cabotegravir • Intravaginal rings – Phase 3 • Dapivirine – Phase 1/2 • Tenofovir • Tenofovir disoproxil fumarate • Vicriviroc + MK 2048 • Dapivirine + Levonorgestrol The PrEP Landscape in 2016 (3) • Rectal microbicides – Phase 2 • Reduced glycerin tenofovir gel – Phase 1 • Maraviroc • Dapivirine • Griffithsin • MIV-150 / Carageenan / Zinc • Implantable PrEP MTN Highlights from the Past Year The MTN Portfolio 2015 / 2016 Studies in Ongoing development: Completed studies MTN-026 studies MTN-030 MTN-015 MTN-031 MTN-017 MTN-016 MTN-032 MTN-020 MTN-023 MTN-033 MTN-024 MTN-027 MTN-028 MTN-034 MTN-029 MTN-035 MTN-036 MTN-037 Intravaginal Ring Studies • Dapivirine • Vicriviroc / MK-2048 – MTN-020 – MTN-027 & MTN-028 – MTN-023 • Dapivirine 200 mg – MTN-025 (HOPE) IVR – MTN-029 – MTN-036 / IPM 047 – MTN-031 – MTN-034 • Dapivirine / Levonorgestrel – MTN-030 / IPM 041 Rectal Microbicide Studies • Tenofovir gel – MTN-017 • Dapivirine gel – MTN-026 – MTN-033 – MTN-035 CHARM-02 Study (Hiruy H et al. AIDS Res Hum Retroviruses 2015) Network Collaboration • HPTN-069 / ACTG 5305 • Phase 2 evaluation of maraviroc based PrEP regimens • Approximately 400 men and 200 women enrolled in the study • MTN contribution – CCR5 genotyping – Gut associated lymphoid tissue flow cytometry – Gut and cervicovaginal explant challenge Explant Infection (P<0.05) (P<0.05) 1 p24 (pg/mL) - HIV CROI 2016 Publications Publications Challenges for the Year Ahead Understanding Suboptimal PrEP Efficacy in Young Women • Differential non- adherence? • Biological vulnerability? • Compartmental pharmacokinetics? • Sexual behavior? Dapivirine Cervical Plasma and – STIs? Ectropion Ring PK by age – Anal sex? Rectal Microbicides • Are rectal microbicides needed with increased access to PrEP? • Can we develop products that do not require an applicator? • Which product (s) should be advanced into Phase 3 effectiveness studies? • What would these studies look like? $$ Managing The MTN Pipeline $$ • MTN-025 (HOPE): DPV IVR Phase 3B • MTN-026: DPV gel rectal Phase 1 • MTN-030 (IPM 041): DPV ± LNG IVR • MTN-031 (IPM 043): DPV IVR ± incentives • MTN-033 (IPM 044): Rectal DPV ± applicator • MTN-034 (IPM 045): DPV versus Truvada • MTN-035: Oral Truvada + rectal DPV gel • MTN-036 (IPM 047): 200 mg DPV IVR • MTN-037: MIV-150/Carageenan/Zinc rectal Phase 1 For This Week • Hear about the latest developments in HIV prevention research during the plenaries – News from CROI: Rings and beyond – Pipeline products – Rectal microbicides: Recent news & future plans – Lessons from contraception • Participate in study specific meetings • Don’t forget to come to the Poster reception this evening! It Takes a Village…. Thank You Acknowledgements The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. .